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Abstract

Background: BCG vaccination is associated with a reduction in all-cause infant mortality in high-mortality settings. The underlying mechanisms remain uncertain, but long-term modulation of the innate immune response (trained immunity) may be involved.Methods: Whole-blood specimens, collected 7 days after randomization from 212 neonates enrolled in a randomized trial of neonatal BCG vaccination, were stimulated with killed pathogens and Toll-like receptor (TLR) ligands to interrogate cytokine responses.Results: -vaccinated infants had increased production of interleukin 6 (IL-6) in unstimulated samples and decreased production of interleukin 1 receptor antagonist, IL-6, and IL-10 and the chemokines macrophage inflammatory protein 1α (MIP-1α),MIP-1β, and monocyte chemoattractant protein 1 (MCP-1) following stimulation with peptidoglycan (TLR2) and R848 (TLR7/8).BCG-vaccinated infants also had decreased MCP-1 responses following stimulation with heterologous pathogens. Sex and maternalBCG vaccination status interacted with neonatal BCG vaccination.Conclusions: Neonatal BCG vaccination influences cytokine responses to TLR ligands and heterologous pathogens. This effectis characterized by decreased antiinflammatory cytokine and chemokine responses in the context of higher levels of IL-6 in unstimulated samples. This supports the hypothesis that BCG vaccination modulates the innate immune system. Further research is warranted to determine whether there is an association between these findings and the beneficial nonspecific (heterologous) effects ofBCG vaccine on all-cause mortality.

Item Type:	Article
Authors/Creators:	Freyne, B and Donath, S and Germano, S and Gardiner, K and Casalaz, D and Robins-Browne, RM and Amenyogbe, N and Messina, NL and Netea, MG and Flanagan, KL and Kollmann, T and Curtis, N
Keywords:	Bacille Calmette-Guérin, immunisation, heterologous, nonspecific, trained immunity
Journal or Publication Title:	Journal of Infectious Diseases
Publisher:	University of Chicago Press
ISSN:	0022-1899
DOI / ID Number:	https://doi.org/10.1093/infdis/jiy069
Copyright Information:	Copyright 2018 The Authors.
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